The research will investigate longitudinally the development and persistence of T, B, and NK cell function in infants and children with human severe combined immunodeficiency (SCID) who are or who become HLA-identical or haploidentical stem cell chimeras. The unique study population will consist of 101 surviving SCIDs who have been given bone marrow stem cells without pre-transplant chemotherapy or post-transplant GVHD prophylaxis. The first aim is to examine longitudinally the phenotypes, functions and genetic origins of T cells in the 101 surviving SCID recipients of HLA-identical (n= l5) or haploidentical (n=86) T cell-depleted parental marrow stem cells post-transplantation. Three hypotheses will be tested: a) that the decline in T cell function with time is associated with phenotypic changes in the genetically-donor T cells suggestive of regulatory T cell dominance, b) that the latter cells will dampen the responsiveness of CD4+CD25- T cells, c) that the degree of HLA matching between the donor and recipient initially will be predictive of whether this pattern is seen, and d) that these T cells arise as a mechanism of maintaining tolerance of the haploidentical donor-derived T cells to the patients' non-shared HLA antigens. The second aim is to examine the role of donor-versus-recipient natural killer (NK) cell alloreactivity in determining marrow allograft acceptance and whether GVHD occurs. Two hypotheses will be tested initially: a) that the presence of HLA Class I mismatches between the donor and recipient in the direction of GVHD correlates with good graft acceptance, and b) that the presence of HLA Class I mismatches between the donor and recipient in the direction of GVHD correlates with the development of no or low grade GVHD. The third aim is to assess the role of abnormal dendritic cell function in the development and persistence of NK cells post-transplantation in X-linked and Jak3-deficient SCIDs. The hypothesis to be tested is that NK cell numbers and function will decline with time after stem cell transplantation in these two types of SCIDs due to abnormalIL-15-dependent dendritic cell (DC) functions. The fourth aim is to continue to investigate the molecular bases of the 18% of SCIDs for whom the cause remains unknown. The hypotheses to be tested are 1) that the lymphocyte phenotype will facilitate the search for known or unknown genes that cause SCID and 2) that the molecular form of SCID will influence the development and persistence of immunity post-transplantation.